title: The mechanism for the ameliorative effect of CpG-oligodeoxynucleotides on bone marrow hemopoiesis radiation injury.
abstract: Bone marrow is a major site of radiation injury. The extreme sensitivity of bone marrow cells to genotoxic stress largely determines the adverse side effects of radiation. CpG-oligodeoxynucleotide (ODN) is known to be radioprotective in extramedullary hemopoiesis, but its effect on bone marrow hemopoiesis remains unknown. In this study, we investigated whether CpG-ODN ameliorated hemopoiesis radiation injury when administered after total-body irradiation (TBI). Mice were treated with 50 μg of CpG-ODN via intraperitoneal injection (i.p) 30 min., 24 and 48 hr after TBI. Our results show that CpG-ODN was able to mediate the activation of nuclear factor κB (NF-κB) via degradation of inhibitor NF-κB (IκB-α), and some oxidative stress parameters (malondialdehyde, glutathione and superoxide dismutase) showed significant differences between the radiation control group and the radiation and administration of CpG-ODN group. White blood cell count, bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized bone marrow damage induced by radiation. Exogenous colony-forming unit-spleen count indicated that CpG-ODN reduced primitive hemopoietic stem cell damage and reconstituted the hemopoietic system after TBI. The survival of mice was also enhanced after various levels of TBI. The calculated dose reduction factor was 1.2. Thus, we conclude that CpG-ODN may contribute to the amelioration of hemopoiesis radiation injury.
authors.affiliation: Section of Radiation Medicine, Department of Naval Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Ni
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.forename: Ding
authors.initials: D
authors.lastname: Sun
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013534:Survival; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D009838:Oligodeoxyribonucleotides; D011837:Radiation-Protective Agents; D000072000:NF-KappaB Inhibitor alpha